Development of a Patient-Derived Xenograft (PDX) of Breast Cancer Bone Metastasis in a Zebrafish Model

Bone metastasis is a complex process that needs to be better understood in order to help clinicians prevent and treat it. Xenografts using patient-derived material (PDX) rather than cancer cell lines are a novel approach that guarantees more clinically realistic results. A primary culture of bone me...

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Bibliographic Details
Published in:International journal of molecular sciences 2016-08, Vol.17 (8), p.1375-1375
Main Authors: Mercatali, Laura, La Manna, Federico, Groenewoud, Arwin, Casadei, Roberto, Recine, Federica, Miserocchi, Giacomo, Pieri, Federica, Liverani, Chiara, Bongiovanni, Alberto, Spadazzi, Chiara, de Vita, Alessandro, van der Pluijm, Gabri, Giorgini, Andrea, Biagini, Roberto, Amadori, Dino, Ibrahim, Toni, Snaar-Jagalska, Ewa
Format: Article
Language:English
Subjects:
Animals
Bone cancer
bone metastasis
Bone Neoplasms - secondary
Breast cancer
Breast Neoplasms - complications
Danio rerio
Disease Models, Animal
Embryos
Female
Fish
Heterografts
Humans
Metastasis
patient-derived xenograft
Xenograft Model Antitumor Assays
Zebrafish
zebrafish model
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Summary:Bone metastasis is a complex process that needs to be better understood in order to help clinicians prevent and treat it. Xenografts using patient-derived material (PDX) rather than cancer cell lines are a novel approach that guarantees more clinically realistic results. A primary culture of bone metastasis derived from a 67-year-old patient with breast cancer was cultured and then injected into zebrafish (ZF) embryos to study its metastatic potential. In vivo behavior and results of gene expression analyses of the primary culture were compared with those of cancer cell lines with different metastatic potential (MCF7 and MDA-MB-231). The MCF7 cell line, which has the same hormonal receptor status as the bone metastasis primary culture, did not survive in the in vivo model. Conversely, MDA-MB-231 disseminated and colonized different parts of the ZF, including caudal hematopoietic tissues (CHT), revealing a migratory phenotype. Primary culture cells disseminated and in later stages extravasated from the vessels, engrafting into ZF tissues and reaching the CHT. Primary cell behavior reflected the clinical course of the patient's medical history. Our results underline the potential for using PDX models in bone metastasis research and outline new methods for the clinical application of this in vivo model.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms17081375